Addressing physical activity (PA) barriers is an essential component of increasing PA among the 56-73% of community-dwelling adults 50 years and older who are not performing the recommended 150 minutes of moderate-to-vigorous PA. As there is no feasible, multi-factorial tool to assess PA barriers among this population, we developed and validated a PA barrier assessment tool called the Inventory of Physical Activity Barriers (IPAB). We collected cross-sectional data on 503 adults (mean age 70.1), with 79 participants completing the scale twice for test-retest reliability and 64 completing a cross-over design examining the ability to use two administration formats interchangeably. Our analyses consisted of exploratory and confirmatory factor analysis, Cronbach alpha, intraclass correlation coefficient, Bland-Altman Plot, and t-tests. Using factor analysis, we identified and confirmed an eight-factor solution consisting of 27 items. The 27-item IPAB is internally consistent , has a high test-retest reliability (intraclass correlation coefficient=0.99), and can differentiate between individuals who meet the recommended levels of PA and those who do not (p < 0.001). The IPAB scores ranged between 1.00-3.11 for the paper format (mean=1.78) and 1.07-3.48 for the electronic format (mean=1.78), with no statistical difference between the paper and electronic administration formats (p=0.94), resulting in the conclusion that the two administration formats can be used interchangeably. Participant feedback illustrates that the IPAB is easy to use, has clear instruction, and is an appropriate length. The newly validated IPAB scale can be used to develop individualized PA interventions that address PA barriers among patients 50 years and older.


Human and veterinary pharmaceuticals are being increasingly used for disease treatment; hence, their distribution and factors influencing them in the aquatic environment need to be investigated. This study observed the effect of human and animal populations, usage, purchasing criteria (prescription vs. non-prescription), and land use to identify the spatio-temporal distribution of eight pharmaceuticals at twenty-four sites of the tributaries of the Han River watershed. In rural areas, the mean concentration (detection frequency) of non-prescription pharmaceuticals (NPPs) was higher (lower) compared to that of prescription pharmaceuticals (PPs); in urban areas, a reverse trend was observed. Pharmaceutical concentrations in urban and rural areas were mainly affected by wastewater treatment plants (WWTPs) and non-point sources, respectively; concentrations were higher downstream (4.9 times) than upstream of the WWTPs. The concentration distribution (according to the target) was as follows: human–veterinary > human > veterinary. Correlation between total concentration and total usage of the pharmaceuticals was high, except for NPPs. Most livestock and land use (except cropland) were significantly positively correlated with pharmaceutical concentrations. Concentrations were mainly higher (1.5 times) during cold seasons than during warm seasons. The results of this study can assist policymakers in managing pharmaceutical pollutants while prioritizing emerging pollutants. Pharmaceuticals, including non-steroidal anti-inflammatory drugs (NSAIDs) and antibiotics, are used for treating human and animal diseases but are considered emerging pollutants, categorized into two classes ,2. PrescVarious factors influence the distribution patterns of pharmaceuticals in urban and rural surface water, including intake and usage patterns ,16,17, pUnfortunately, large quantities of pharmaceuticals in surface water can endanger aquatic organisms such as bacteria, algae, invertebrate, and fish. Biotoxicity and susceptibility of organisms to the pharmaceuticals vary depending on the compounds and species ,34,35,36While pharmaceuticals can affect water environments in various ways ,51, theiStudies have identified that WWTPs affect the distribution of pharmaceutical concentrations in surface water of the Han River watershed, yet, other factors affecting the distribution have not been identified ,54,55,56In the present study, we discuss the results from a field study conducted from October 2015 to September 2016. The main objectives of this study were to: (1) investigate the overall distribution trend of eight pharmaceuticals; (2) compare PPs and NPPs at upstream and downstream areas of WWTPs; (3) identify the effects of human and animal populations, drug use (prescription and non-prescription), and land use on the distribution of the pharmaceuticals and the respective correlations; (4) describe the spatio-temporal variations in pharmaceutical concentrations and their possible pollutant sources in the tributaries of the Han River watershed, South Korea.4 (SMZ-d4), and ibuprofen-d3 (IBP-d3), were purchased from Toronto Research Chemicals . HPLC grade solvents such as methanol and acetonitrile, and Na2-EDTA  were obtained from Sigma-Aldrich. Reagent water was prepared by Milli-Q water purification system . Individual stock solutions of each compound were prepared in methanol; standard mixtures were prepared by diluting the stock solution and stored in the dark at –20 °C. All glassware were baked at 250 °C overnight in the oven, and rinsed with methanol prior to use.Eight pharmaceutical compounds (purity > 98%): naproxen (NPX), acetylsalicylic acid (ASA), carbamazepine (CBZ), trimethoprim (TMP), clarithromycin (CTM), sulfamethazine (SMZ), sulfamethoxazole (SMX), and sulfathiazole (STZ) were purchased from Sigma-Aldrich . The details of these pharmaceutical compounds are given in The Han River watershed is the largest in South Korea, consisting of four major rivers  and includes Seoul  and Gyeonggi Province . Several tributaries flowing into the Han River are impacted by human activities in Seoul. In this study, human and livestock population and land use data were retrieved from the Korean Statistical Information Service (KOSIS) . For thi3/day), were identified; details are presented in Twenty-five WWTPs, except for those with a small treatment capacity (<1.0 m2-EDTA in water. Oasis HLB (500 mg–6 mL) solid phase extraction (SPE) cartridges were used to extract the compounds from the water samples. Preconditioning of cartridges was carried out in the following order: 4 mL water → 4 mL methanol → 4 mL water → 5 mL water . The sample was loaded at a rate of about 10 mL/min using SPE cartridges after conditioning. Cartridges were washed with 6 mL acidified water to extract any residual Na2-EDTA prior to drying under vacuum, for approximately 1 h. Analytes were eluted with 6 mL methanol and 12 mL of methanol/acetone . The extracts were evaporated to 0.5–1 mL with a gentle stream of high-purity N2.Water samples (2 × 500 mL), filtered using 0.22 µm cellulose acetate membrane , were spiked with 25 µL isotopically labeled standard mix and 1000 µL of NaTM, Milford, MA, USA) equipped with an Agilent Eclipse plus C18 column . The eluent flow rate was 0.25 mL/min with a gradient of eluent A (acetonitrile) and B (5 mM ammonium acetate). The gradient program was as follows: 15% A to 2 min, linear increase of B, A to 90% in 3 min and held for 2 min. The total run time was 15 min. A returned to 15% in 3 min and was stabilized for 5 min to finish the cycle. Injection volume of 10 µL was used for analysis and the column temperature was maintained at 40 °C. For MS detection, the instrument was operated in the positive electrospray ionization and multiple reactions monitoring (MRM) mode. The MS/MS parameters were optimized as follows: nebulizer pressure, 35 psi; gas flow, 8 L min−1; mass range, 100–400 amu; scan time, 300 ms; temperature, 350 °C. Other parameters of MS/MS and retention time are summarized in The eight pharmaceuticals and ISs were quantified by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) coupled to Quattro Premier MS . Detailed information is given in The pharmaceuticals’ method detection limit (MDL) and limit of quantitation (LOQ), classified as the concentrations corresponding to the signal-to-noise (S/N) ratios of 3 and 10, respectively, were 0.0008–0.013 µg/L and 0.0026–0.0413 µg/L, with spiked concentration between 0.005 µg/L and 0.03 µg/L. The pharmaceutical recovery and precision rate for the filtered surface water samples ranged from 91.2% to 113.7% and 1.8% to 15.2% for all analytes. The calibration curve was generated over a broad concentration range (0.2–1000 µg/L) to demonstrate high linearity  was used to generate graphics, and ArcGIS 9.2  was used to produce a digital map of the Han River watershed.Minitab 15  and Excel 2016  were used to conduct the statistical analysis. Pearson’s correlation analysis was conducted to identify sources using pharmaceutical concentrations, and one-way analysis of variance (ANOVA) and two-sample paired Concentrations and detection frequencies of the target pharmaceuticals in the tributaries of Han River watershed are shown in ow influences the sorption of different chemicals in WWTPs, pH may also influence sorption behavior; hence, Dow’s pH-dependent n-octanol water distribution ratio was estimated using the median pH 7 observed in this study [ow > 4; Log Dow > 2.5) and have a large molecular weight (MW > 500 g/mol) [ow < 4; Log Dow < 2.5), removal by sorption would be negligible. Although pharmaceuticals are not recalcitrant pollutants in surface water (T ½ = 151.2–1440 h), the importance of continuous discharge should not be overlooked.The distribution of concentration of the pharmaceutical compounds is related to their properties . Althougis study  (Table S0 g/mol) ,72. HoweWhile most pharmaceuticals generally require a prescription, some are readily available at convenience stores without a prescription . TherefoThe high detection frequency of the PPs in both urban and rural areas can be attributed to the continuous discharge from WWTPs (point source), whereas the relatively high mean concentration of NPPs in the rural areas can be attributed to the untreated discharge from public and private facilities such as parks, museums, camping sites, and arboretums, as well as to a floating population ,56,74. AThe concentration of pharmaceuticals upstream and downstream of the WWTPs was examined. Of the twenty-four sites, nine and fifteen sites were present upstream and downstream, respectively. The total concentration and detection frequency downstream of the WWTPs was 4.9- and 2.4-times higher than those upstream, as shown in Pharmaceutical compounds selected in this study are divided into human, human and veterinary, and veterinary according to their intended use and detection concentration . PharmacBy contrast, the relatively high proportion of rural areas and natural tourist attractions can cause the pharmaceuticals to be generated in the form of non-point pollutants, and their high concentrations were detected owing to the low removal efficiency of relatively old and small WWTPs . SMZ, whSun et al.  reportedConcentration of pharmaceuticals in surface water have been reported to be a function of the population, livestock species and number, and land use types, as well as the population not connected to WWTPs as the potential pollutant sources; studies on correlation among these variables have been conducted in different countries ,20,81. Hp < 0.05). In cropland, herbicides and chemicals necessary for farming are mainly used rather than pharmaceuticals; hence, the proportion of pharmaceuticals utilized in the human and veterinary category is relatively very little [y little . Livestoy little . In addiy little  concludeThe concentration distribution of pharmaceutical compounds in independent rivers in the Han River watershed was analyzed . In the HR-4, where the highest pharmaceutical concentration was detected in the HR area, is located directly under the largest WWTP-19 in Seoul; the mean concentration was 10.1 times higher than that at HR-3 which is located upstream on the same river and is not affected by WWTPs. The pharmaceutical concentration in the HR area was found to be in the following order: HR-4 > -5 > -2 > -7 > -1 > -6 > -3 ranging from 0.0042 µg/L to 0.8661 µg/L with 12.5–75.0% detection frequency.The second highest pharmaceutical concentration and detection frequency were in found in the IHR area. IHR-1 was detected having the second highest concentration among the 24 sites. However, unlike HR-4, this site does not have a WWTP located upstream, but a large recreational park is located nearby. This park is considered a non-point pollution source, unlike the WWTPs, which is a point source of pollution. Poor park management and careless waste discharge (such as that from toilet facilities) can lead to pharmaceutical compounds being present in high concentrations in the nearby areas. Other sites, IHR-2, -3, and -4, similarly detected low concentrations ranging from 0.0052 µg/L to 0.0859 µg/L.The third highest concentration was detected in the SR area. SR-6 and -7 are not characterized by a WWTP upstream; they showed the lowest concentrations of pharmaceuticals while relatively high concentrations were detected at SR-4. Due to the mixed impact of non-point pollution sources such as livestock and farming, the Bok River, where SR-4 is located, receives pollutants from non-point sources such as livestock and farming . Two WWTThe NR area was characterized by the least amounts of pharmaceutical compounds among the areas studied; each site had very low levels of pollutants. The concentration of pharmaceutical compounds was different at each site in each river, and this is attributed to the capacity of WWTPs, the removal rate of pollutants by the WWTPs, and the content of organic matter in the WWTP effluent .The water temperature was divided into cold  and warm , corresponding to the seasons, and the concentration of pharmaceutical compounds in each season is shown in This study has several strengths and limitations. First, to the best of our knowledge, this is the first study to identify the distribution characteristics of prescription and non-prescription pharmaceuticals in tributaries of the Han River. Second, we found that pharmaceuticals originated from human and animal populations and drug and land use. Third, we demonstrated high-quality analytical performance  due to proper equipment maintenance during the analysis of pharmaceuticals in surface water samples. These results provide insight into the distribution of pharmaceutical substances in surface water based on environmental factors.However, some limitations should be considered when interpreting our findings. First, a total of four water samples may not reflect the concentration of general pharmaceutical compounds representing the Han River watershed. Although sampling was performed at the same place and time, no data were collected for unusual environmental events, such as heavy rain and water structure construction. Second, confounding factors, such as regional pharmaceutical usage, an aging population, and major diseases may affect the results of this study. These factors could be the focus of future research.Therefore, continued research and data collection will inform policymakers, securing the health of the aquatic ecosystem in surface water. Moreover, policymakers can use the comprehensive results of this study to determine the concentration and detection frequency of pharmaceuticals in the Han River watershed and consider the possibility of pharmaceutical discharge due to environmental factors.p < 0.05). Higher concentrations were mainly observed during the cold season, with the mean concentration being 1.3 times higher than that during the warm season. Spatial analysis revealed that the pharmaceutical concentrations in different areas were impacted by different sources. This study provides scientific information to policymakers for regulating the concentrations of pharmaceutical pollutants in natural aquatic environments, as well as identifying priority emerging pollutants.In this study, eight pharmaceutical compounds of different therapeutic classes were investigated at twenty-four sites of the tributaries in the Han River watershed. The effects of various factors on pharmaceuticals distribution were investigated. Each of the studied pharmaceuticals were detected at least once in all of the samples. The mean concentrations of the pharmaceuticals showed the following order: CTM > NPX > CBZ > ASA > TMP > SMX > SMN > STZ with detection frequency ranging from 6.3% to 78.1%. In urban areas, the mean concentration and detection frequency of the PPs were higher than those of the NPPs, and in urban and rural areas, the pharmaceutical concentrations were significantly higher downstream of the WWTPs than upstream; this is mainly attributed to the WWTPs. Overall, human and human–veterinary pharmaceuticals were more abundant and were measured in higher concentrations compared to the veterinary pharmaceuticals. All livestock and land use (except cropland) were found to have a significant positive correlation with the concentration of pharmaceuticals (


Consumer choice models have been introduced in eldercare services in several Western welfare societies. Choice models in eldercare emphasise the importance of individuals’ abilities to make informed choices and therefore entail a risk for increased inequalities among older adults with care needs. In the Nordic countries, such inequality risks are in stark contrast to universal policy ambitions of equal access to care services. Care managers, who are responsible for needs assessment for eldercare services, have a central role in implementing policies and, thus, have first-hand experience of their impact on older adults’ access to care. The aim of this study was to explore care managers’ experiences of how user choice affects older adults’ access to care services in three Nordic cities: Copenhagen, Tampere, and Stockholm. These cities were purposely selected as forerunners in marketisation, with different ways of implementing choice models. Semi-structured interviews with care managers were conducted in Copenhagen, Tampere, and Stockholm and analysed thematically. The findings indicate there are difficulties related to older adults’ ability to access information needed to make informed choices, as well as limitations in choice related to available services and personal finances. Further, care managers find that older adults’ abilities to overcome these difficulties are shaped by their health, education, language skills, and assistance from relatives. In order to reduce the risk of choice models increasing the gap between older adults with different resources and capabilities, there is a need to develop accessible information, as well as models for professional guidance. Choice models have reorganised the provision of long-term care (LTC) across all Western societies  providers in both home care and residential care. Distinctive for Stockholm was the large number of service providers. For example, a home care user could choose between more than 60 providers in each city district.According to the law regulating choice models, the Act of System of Choice, local authorities have to appoint a provider, which could be public or private, for those who do not choose for themselves . Users could also choose a ‘self-appointed carer’, who was employed by the municipality after an assessment of the carer’s qualifications. In Denmark, the Law on Free Choice of Provider of Practical Assistance and Personal Care has obliged local authorities to adopt choice models in home care since 2003, whereas it was optional in residential care  to make informed choices  or personal (help with the body). As a consequence, there was a general lack of services addressing social needs, as one care manager in Copenhagen illustrated: ‘There are those who have needs related to loneliness or anxiety, and it’s really hard to support them with that. We have no services aimed at these needs.’The standardisation of services entails difficulties in meeting complex needs, such as mental health problems and substance abuse in combination with physical problems or dementia. In all three cities, care managers stated that it is hard to meet needs that do not match the available services. A care manager in Tampere concluded: ‘I am quite helpless because I have no services to offer them.’When it comes to having services granted, relatives can be of importance. Care managers reported that older adults who have relatives who know what services there are and what arguments to use in order to get these services are in a better position to receive services since these relatives tend to act as advocates for their next-of-kin and argue their case for them. This is especially so if the older adults are on the verge of being eligible for a service, as illustrated by a care manager in Copenhagen: ‘Sometimes, you might give in a little, and it might be a little easier to grant the service than if nobody is pushing for it.’ In line with this, care managers expressed concerns that older adults who do not have relatives to inform them might miss out on services because they are unaware of them.Another aspect of limitations in choice regarded personal finances. This subject was most commonly raised by care managers in Tampere, where older adults with enough financial resources could access choices either through the private market for home care services or through the voucher system for residential care. One care manager explained the importance of personal finances: ‘What gives you options is money. If you receive a low pension and you only have a little bit of money at your disposal, then you don’t have that freedom of choice.’However, the importance of personal finances extends beyond the choice model in Tampere, where care managers experienced that older adults cut back on services or even refrained from services due to high customer fees, even for public services. One care manager in Tampere illustrated: ‘Yesterday, I received a call from a customer who had just started receiving a service. The customer told me their monthly income, and I calculated what the monthly fee would be. The customer was terrified and had to cut back on the services.’Care managers in Stockholm had also experienced users being reluctant to accept services due to user fees, although they did not report this to the same extent as the care managers in Tampere. In Stockholm, this was perceived as most common among users with smaller care needs, who felt that the costs for services were disproportionally high. One care manager in Stockholm said: ‘There are some who think they cannot afford it, that their financial situation would become too strained. And they sometimes decline services.’ In Copenhagen, where there were no fees for home care services, the care managers did not report that financial resources affected access to care services.Care managers rarely mentioned any positive aspects of choice models, and when they did, there was no consistency between the cities. In Stockholm, care managers declared the emergence of providers with different language profiles to be an improvement for older migrants since the opportunity to receive care in one’s own language makes services more accessible. One care manager in Stockholm said: ‘Then they can understand the staff because they speak the same language. So, it is very beneficial that there are different providers of home care services who know different languages.’ However, other care managers problematised that this opportunity was only present for some of the largest language groups, and the providers usually made no guarantees that all staff could speak a specific language.In Tampere, the city where older adults’ personal finances mattered the most, some of the care managers emphasised that the choice model benefited older adults with a good personal economy. However, they approached this fact from different perspectives. As shown in the section on personal finances, some expressed concern for those least well off. Others argued that it is only fair that people with more money can access more or better services. When discussing the voucher for residential care services, which is only available for the more well off, one care manager in Tampere stated: ‘Why should everybody have the same ‘shit’, so to speak? Why shouldn’t everyone who has money use it for their own well-being? I think it is a great addition.’This paper has explored care managers’ experiences of how choice models affect older adults’ access to LTC in three Nordic cities. The findings suggest that choice models entail more difficulties than benefits. Across all cities, the findings revealed difficulties related to accessing information needed to make informed choices. These difficulties are related to the fact that the information older adults receive in relation to making choices is general, while older adults are expected to find more specific information needed to make informed choices by themselves. In line with earlier studies, the care managers in our study stressed that difficulties in accessing information are exacerbated when the older adult is in a poor state of health and has a lack of energy and/or reduced cognitive capacity  or personal (help with the body), which means that people with complex needs and social needs, such as loneliness, are disadvantaged. However, these problems are more related to cutbacks and standardisation of services (Kröger and Leinonen Taken together, these findings have implications for two different aspects of inequality in access to care: unequal opportunities to make informed choices and unequal opportunities to having ones needs met. This shows that sameness in treatment is not enough to achieve equality in outcomes Fineman , 2017. EThe differences between the cities regarding the benefits of choice models and the importance of financial resources show that choice models may have different implications in different contexts. The large number of providers in Stockholm can be an obstacle in choice but also entails the benefit of providers with language profiles. Most variation between the cities is related to the importance of personal finances. In Tampere, the impact of personal income seems much more prominent than in the other cities. This can be attributed to high user fees in publicly funded Finnish LTC, in combination with a voucher system for residential care that is only accessible for those with a solid personal economy. Also, in Stockholm, the care managers experienced that older adults with fewer resources struggle with the user fees. In Denmark, there are no fees for home care services, and care managers in Copenhagen did not perceive personal finances as a barrier to care. The fact that care mangers experience that user fees restrict access to LTC in two of the three cities is worrying from an equality perspective, and deserves more attention in the future research.Altogether, the findings indicate that the operations and organisations of choice models reproduce existing inequalities (cf. Fineman In addition, the findings of this study point to the conclusion that general knowledge of the welfare system is an advantage, whereas newcomers to the system, such as older migrants, are disadvantaged. Although non-native speakers are generally identified as a disadvantaged group in research on choice models (cf. Baxter et al. One limitation of this study is that we only present the perspectives of care managers and, thus, have no empirical data of older adults’ experiences. By interviewing older adults about their experiences, we could have gained insight into individual experiences of choice models. However, interviewing care managers, who meet many older adults in their work, provided an overview of how choice models affect access to services. Another limitation is that we rely solely on interview data reflecting the care managers’ experiences, which means we cannot determine actual differences in older adults’ access to LTC within, or between, the three cities. Despite these limitations, the study points to significant design flaws and contributes to the knowledge on inequality implications of the interplay between how choice models are implemented and general features of LTC.In line with other studies, our findings suggest that older adults have different resources and abilities to overcome barriers raised by design flaws. Like Fineman , we percThe present study has identified general system design features that could potentially ameliorate inequalities among older adults: low user fees, services that match actual needs and not only the most basic ones, and more transparent choice models with tailored information. There is also a need for more targeted interventions, such as information in different formats, including easy-to-read formats; information in foreign languages; and professional guidance for those who do not have a network of relatives to rely on, as well as other vulnerable groups, such as non-native speakers and people with dementia (cf. Baxter et al. The findings revealed difficulties related to design features of choice models but also difficulties that are not directly related to choice models. According to care managers, older adults with poor health, low education, poor language skills, and no close relatives are the most negatively affected by these difficulties. To prevent the gap from increasing between older adults with greater resources and those with fewer resources, measures are needed to make LTC more transparent and accessible for everyone.


Patients successfully resuscitated from cardiac arrest often develop organ dysfunction caused by systemic inflammation and increased coagulation, leading to disseminated intravascular coagulation (DIC). The involvement of histones in DIC and organ dysfunction in patients with sepsis and trauma has been previously reported, raising the probability that histones may also be associated with pathophysiology in patients after cardiac arrest and resuscitation. This study evaluated the relationship between histones and organ dysfunction related to coagulofibrinolytic changes in patients with post-cardiac arrest syndrome (PCAS).This prospective single-center observational study assessed 35 adult patients with PCAS who were divided into two groups, i.e., 15 patients with multiple organ dysfunction syndrome (MODS) and 20 patients without MODS. MODS was defined as a sequential organ failure assessment score of ≥12. The plasma levels of histones and coagulofibrinolytic markers, including soluble fibrin, tissue-type plasminogen activator, plasminogen activator inhibitor-1, plasmin-alpha 2-plasmin inhibitor complex (PIC), and soluble thrombomodulin, were measured in patients with PCAS immediately after admission to the emergency department, and 3 and 24 h after arriving at the hospital.p = 0.012] and higher mortality rates  than those without MODS. Moreover, patients with MODS exhibited higher histone levels than those without MODS during the early phase of the post-resuscitation period. Severe endothelial injury and higher thrombin and plasmin generation were observed in the MODS group. Plasma levels of histones were positively correlated with those of soluble fibrin immediately after resuscitation  and PIC 3 h after arriving at the hospital . This correlation was prominent in the patient population with MODS .PCAS patients with MODS had higher DIC scores [4 (3.0–5.0) vs. 1 (0.0–3.0), This study demonstrated that elevated histone levels were associated with increased levels of thrombin, and subsequent plasmin generation in PCAS patients, especially those with MODS. Further studies are required to elucidate the causal relationship between histones and organ dysfunction related to DIC in PCAS. Over the past half-century, the rate of return of spontaneous circulation (ROSC) has considerably improved owing to the widespread use of cardiopulmonary resuscitation (CPR) among the public and advances in treatment methods for patients after cardiac arrest. However, the long-term survival of resuscitated patients remains poor. The high mortality rate in patients who are successfully resuscitated after cardiac arrest may be ascribed to the development of post-cardiac arrest syndrome (PCAS) . The IntRecent studies have shown the importance of bidirectional interactions between inflammation and coagulation that are triggered by damage-associated molecular patterns (DAMPs), such as histones— in response to cellular injury and neutrophil extracellular traps (NETs) released by activated neutrophils—in the pathophysiology of DIC , 8. AlthWe conducted a single-center prospective observational study. A total of 47 patients who experienced out-of-hospital cardiac arrest were enrolled between September 2018 and June 2020. Patients were excluded if they did not achieve ROSC or were under 20 years of age. Written informed consent was obtained from the patients' next of kin to draw blood samples and record essential data necessary for scoring DIC, acute physiology and acute chronic health evaluation (APACHE) II, and sequential organ failure assessment (SOFA) scores. If the next of kin did not accompany any of the patients, informed consent was retrospectively obtained after collecting blood samples at 0 h. In addition, blood samples from 15 healthy volunteers , who were medical students and medical staff in our hospital), were collected to measure plasma levels of histones and coagulofibrinolytic markers. The study was approved by the Institutional Review Board of the Ethics Committee of Hokkaido University School of Medicine (017-0518).DIC was diagnosed according to the Japanese Association for Acute Medicine (JAAM) DIC score  14). Th. Th14). Blood samples were collected from an arterial catheter in patients using a syringe at three-time points: immediately after ROSC (0 h), 3 h after ROSC (3 h), and 24 h after ROSC (24 h). Blood samples from healthy volunteers were collected once per person. Blood samples were immediately placed into tubes with sodium citrate and centrifuged at 1,500 × g for 15 min at 4°C. The plasma was stored at −80°C until further examination.We measured the plasma levels of histones   and the Data necessary for scoring such as DIC score, SOFA score, APACHE II score, and other general coagulation markers, including antithrombin, fibrinogen/fibrin degradation products (FDPs), and D-dimer were retrieved from the medical records.U-test. Categorical data were compared among the groups using Fisher's exact test or Pearson's chi-squared test, depending on the size of the data. Correlations were evaluated using Spearman's rank test. Receiver operating characteristic (ROC) curve analyses with the area under the curve (AUC) calculation were used to quantify the predictive performance of the plasma levels of histones at each time point. Statistical significance was set at P < 0.05. All statistical analyses and calculations were performed using GraphPad Prism for Windows version 9.3.1  and JMP Pro 16.0 .Numerical variables were presented as medians and quartiles, and categorical variables were summarized as numbers and percentages. Numerical data were compared among groups using the two-sided non-parametric Mann–Whitney n = 15) and non-MODS (n = 20) groups. The characteristics of the patients in both groups are shown in Out of the 47 patients, 12 were excluded from the study. Among the excluded patients, 11 did not achieve ROSC. We also excluded one patient because the samples were not treated appropriately. In the present study, we analyzed the final cohort of 35 patients. The patients were divided into MODS . There were no significant differences in PAI-1 levels at any time point between the MODS and non-MODS groups, whereas PAI-1 levels at 24 h in the MODS group tended to be higher than those in the non-MODS group.Serial changes in coagulofibrinolytic molecular markers  are shown in p = 0.030). This correlation was prominent in a population with MODS . There was also a positive correlation between histone levels and PIC measured at 3 h, when the fibrinolysis is considered to peak . This correlation became stronger in the MODS group.We evaluated the correlation between plasma levels of histones and coagulofibrinolytic markers . There w to peak , 22,  curves. The area under the curve (AUC) for plasma levels of histones measured at 0 was 0.710  . In ordeIn the current study, we found that PCAS patients with MODS had higher DIC scores and higher mortality rates than those without MODS. In addition, patients with MODS exhibited massive thrombin and plasmin generation with higher levels of histones than those without MODS during the acute phase of PCAS. The levels of histones were positively correlated with SF, a thrombin generation marker, and PIC, a plasmin generation marker. According to our analysis, the plasma level of histones immediately after ROSC was a good predictor of MODS development in patients with PCAS.Histones are commonly known as DNA-binding proteins that play an important role in compacting DNA to be stored in the nucleus –25. HistA previous study demonstrated that the levels of circulating histones increase in mouse models of sepsis in a neutrophil-dependent manner, suggesting that histones are mainly derived from NETs . HoweverAlthough this study cannot demonstrate a causal relationship between histones and the pathophysiology of PCAS-associated DIC, we believe that extracellular histones may be a promising therapeutic target for PCAS-associated coagulopathy and consequent organ dysfunction, as previous studies showed that the administration of neutralizing antibodies to histones can prevent death from severe sepsis in a murine model , 28. ThiThis study has several limitations. First, we excluded 11 patients without ROSC from initial cohort because this study aimed to elucidate the pathophysiology of PCAS. This may be a study limitation. Second, the sample size was small. This limitation may have resulted in wide variations in the measured parameters as shown in To the best of our knowledge, this is the first study to investigate the relationship between histones and the coagulofibrinolytic changes associated with PCAS and to suggest the potential of histones for predicting the MODS development in patients with PCAS. Although the causal relationship between histones and organ dysfunction related to DIC in PCAS requires investigation, we expect that the neutralization of histones may represent a new therapeutic strategy for treating PCAS.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Institutional Review Board of the Ethics Committee of Hokkaido University School of Medicine (017-0518). The patients/participants provided their written informed consent to participate in this study.AM analyzed the study results, interpreted the data, and drafted the manuscript. TW oversaw the entire research and contributed to the research concept, the analysis, and interpretation of the data, and was responsible for drafting, editing, and submitting the manuscript. TT contributed to the data acquisition, interpreted the data, and revised the manuscript for important intellectual content. SG had a significant influence on data interpretation and critical appraisal of the manuscript. All authors read and approved the final version of the manuscript before submission.This work was supported in part by JSPS KAKENHI .The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


All patients received combined immunotherapies (anakinra ± corticosteroids ± intravenous immunoglobulin ± tocilizumab) according to our local treatment algorithm. The endpoint was the composite event of intubation due to severe respiratory failure (SRF) or mortality. Median (interquartile range) sIL-2R levels were significantly higher in patients with severe disease, compared with those with moderate disease (6 (6.2) vs. 5.2 (3.4) ng/mL, p = 0.017). sIL-2R was the strongest laboratory predictive factor for intubation/death  after adjustment for other known risk factors. Youden’s index revealed optimal sIL-2R cut-off for predicting intubation/death at 9 ng/mL . Delta sIL-2R between the day of event or discharge minus admission date was higher in patients that intubated/died than in those who did not experience an event (2.91 (10.42) vs. 0.44 (2.88) ng/mL; p = 0.08)). sIL-2R on admission and its dynamic changes during follow-up may reflect disease severity and predict the development of SRF and mortality.Risk stratification of coronavirus disease-19 (COVID-19) patients by simple markers is critical to guide treatment. We studied the predictive value of soluble interleukin-2 receptor (sIL-2R) for the early identification of patients at risk of developing severe clinical outcomes. sIL-2R levels were measured in 197 patients (60.9% males; median age 61 years; moderate disease,  Coronavirus disease 2019 (COVID-19) has a wide clinical spectrum, ranging from asymptomatic to severe respiratory failure (SRF), multiorgan failure, and death ,4. IndeeEvidence suggests that the pathophysiology of COVID-19 deterioration is based on immune dysregulation and hyperinflammation resembling cytokine release syndrome, driven by several pro-inflammatory cytokines ,9. ExcesHowever, to date, few studies have investigated the correlation between COVID-19 severity and soluble interleukin-2 receptor (sIL-2R), which is one of the biomarkers of immunological dysregulation ,21,22. IAccordingly, the aim of the present study was to determine the predictive value of sIL-2R levels for identifying COVID-19 patients who are at risk of deterioration to severe clinical outcomes as timely initiation of targeted interventions in these patients seems crucial to prevent progression to SRF and reduce mortality.2) ≥ 94%, whereas severe pneumonia was characterised by the presence of at least one of the following: SpO2 < 94% in room air, breath rate > 30/min, respiratory ratio (pO2/FiO2) < 300, and pulmonary infiltrates in more than >50% of the lung parenchyma [sIL-2R levels were measured in the sera of 197 patients  hospitalised in our Department due to moderate or severe pneumonia caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Moderate pneumonia was defined by oxygen saturation by pulse oximetry in room air , and laboratory inflammation markers  were recorded at baseline. All patients were treated with combined immunotherapies (anakinra ± corticosteroids ± intravenous immunoglobulin ± tocilizumab) based on initial ferritin levels and according to our local treatment algorithm [Demographics , smoking habits), comorbidities , cardiovascular diseases), parameters of disease severity , according to the manufacturer’s instructions. Serum samples of patients were collected and stored frozen at −20 °C until use. Samples were thawed only once to prevent repeated freeze–thaw cycles. A standard curve was constructed using 7 standards of twofold serial dilutions from 20 ng/mL to 0.31 ng/mL. To avoid a Hook effect, samples with a concentration greater than the standard of 20 ng/mL were further diluted to precisely quantitate the actual sIL-2R level. The calculated overall intra-assay and inter-assay coefficients of variations were 7.2% and 9.8%, respectively.sIL-2R serum levels were determined by using sIL-2 Receptor Human ELISA , Fisher’s exact test, Spearman’s rho correlation, and binary logistic regression analysis were used to analyse the data. The impact of baseline clinical and laboratory risk factors on our composite endpoint of intubation/mortality was evaluated by univariate and multivariate Cox regression analyses. Receiver operating characteristic (ROC) curves were constructed, and comparisons were performed by the DeLong test. Youden indices (sensitivity + specificity − 1) were calculated to establish optimal cut-offs for sIL-2R. Two-sided p-values less than 0.05 were considered statistically significant. All data analyses were carried out with SPSS version 26.0.The Kolmogorov–Smirnov test was applied to assess the normal distribution of variables, and quantitative values were expressed as median (interquartile range (IQR)). Mann–Whitney U-test, xAmong the 197 patients  with COVID-19 recruited in this study, 92 had moderate and 105 had severe disease at the time of first evaluation. Overall, 27 patients with moderate disease (29.3%) progressed to severe disease during hospitalisation.The demographic, clinical, and laboratory characteristics of patients are summarised in p < 0.001), increased BMI (p = 0.018), higher prevalence of cardiovascular disease (p = 0.001), lower lymphocytes (p = 0.005), and higher CRP (p < 0.001) and ferritin (p < 0.001) levels at the time of presentation.Patients with severe disease were characterised by older age (p = 0.017). sIL-2R levels were negatively correlated with respiratory ratio  and lymphocytes count . A positive correlation was found between sIL-2R and CRP , whereas no correlation was found with ferritin .sIL-2R levels were significantly higher in patients with severe disease (6 (6.2) vs. 5.2 (3.4) ng/mL, During follow-up, 42/197 (21.3%) were intubated or died. p < 0.001); presence of diabetes ; cardiovascular disease ; lower pO2/FiO2 ratio ; decreased lymphocytes count ; increased ferritin ; CRP ; sIL-2R levels .Univariate analysis revealed that intubation/mortality was associated with advanced age : 1.031–1.081, p = 0.030) and low pO2/FiO2 ratio , while only the increased sIL-2R levels maintained a significant negative prediction for intubation or death among the laboratory markers , while a trend was found when compared with CRP levels at baseline (AUC (95%CI): 0.683 (0.594–0.773); p = 0.065) (The AUC (95%CI) of sIL-2R for detecting patients with COVID-19 who eventually intubated or died was 0.789 (0.709–0.869). sIL-2R at presentation had higher predictive ability when compared with ferritin (AUC (95%CI): 0.612 (0.513–0.711); = 0.065) .p < 0.001), lower pO2/FiO2 ratio (p < 0.001), increased respiratory rate (p = 0.008), lower lymphocytes (p = 0.007) and higher CRP levels . Patients with sIL-2R ≥ 9 ng/mL were characterised by increased age . Serum samples were collected at baseline, in the middle of hospitalisation, and at discharge or at the time point of intubation/death. During hospitalisation, 9/23 patients were intubated or died .n = 9) and patients who were discharged from the hospital without intubation (n = 14) showed higher levels for the former group at three different time points: baseline (10.1 (4) vs. 3.7 (2.8) ng/mL; p = 0.001), middle of hospitalisation (9.4 (4.2) vs. 4.9 (4.2) ng/mL; p = 0.002), time of discharge or intubation/death (14.6 (14.2) vs. 3.9 (4) ng/mL; p = 0.002) (p = 0.013) (p = 0.001) (p = 0.109 and lymphocytes: 700 (1040) vs. 845 (670); p = 0.477) and baseline between the two groups of the patients (ferritin: 634 (1862) vs. 458 (533); p = 0.141 and lymphocytes: 900 (525) vs. 1075 (833); p = 0.250)  vs. 0.9 (1.1), p = 0.109, time of intubation/death or discharge: 0.2 (0.7) vs. 0.1 (0.2); p = 0.083) (A comparison of median (IQR) sIL-2R at three different time points between patients who were intubated or died (= 0.002) A. Furthe= 0.013) B and low= 0.001) D only at= 0.250) B,D. No d= 0.083) C.p = 0.08)) (p = 0.011)  delta sIL-2R (day of event or discharge day of admission) was higher in the group of patients that intubated or died (2.91 (10.42) ng/mL), compared with patients who did not experience an event (0.44 (2.88) ng/mL; = 0.08)) A. In add= 0.011) D, while In the current study, we evaluated the relationship between sIL-2R levels and the disease severity of COVID-19 pneumonia and outcomes of patients. Our analysis demonstrated that sIL-2R was associated with severe pneumonia and mainly that sIL-2R levels at baseline were the strongest laboratory-negative predictive factor for patient outcome. According to our results, a level of sIL-2R greater than 9 ng/mL had a PPV of 86% and an NPV of 91% for intubation or death.From the first days of the pandemic, serum concentrations of both anti-inflammatory IL-10) and pro-inflammatory cytokines  were found to be increased in severe cases of COVID-19, compared with patients with moderate disease, implying that a cytokine storm is linked to disease pathogenesis . However0 and proMoreover, several laboratory markers have been thoroughly investigated in an attempt to develop early diagnostic and prognostic biomarkers for predicting COVID-19 progression to severe disease and outcome. In this context, hyperferritinaemia, high CRP levels, and lymphopenia, along with some more sophisticated markers such as the soluble urokinase plasminogen activator receptor (suPAR) ≥ 6 ng/mL and SCOPE score ≥ 6, have already been associated with severity and survival of COVID-19 patients ,34,35,36Notably, in parallel with other reports, we found that sIL-2R levels are negatively associated with lymphocytes count, as has also been shown in previous studies ,22. SeveRegarding the outcome of patients, our data showed that increased sIL-2R levels on admission are associated with increased rates of intubation or mortality. In line with our findings, previous studies have shown that sIL-2R levels are associated with worst outcomes, as attested by longer duration of illness and time to recover, and lower survival rates ,17,18. MMoreover, sequential monitoring of sIL2R may add further diagnostic value for patients who are likely to bear poor prognoses. Indeed, according to our subanalysis, individuals who were intubated or died had consistently higher levels of sIL-2R during hospitalisation, compared with patients who did not experience an event, while ferritin and lymphocytes differ only at the time point of the event, which attenuates their predictive values. Moreover, the increase in sIL-2R levels was higher in patients with an unfavourable course of the disease.Indeed, future research is needed to evaluate the relationship between sIL-2R serum levels and immunological response to various stimuli in COVID-19 patients; however, the cross-sectional design of our study did not allow us to conduct such tests.In conclusion, the simple determination of sIL-2R on admission by an easy-to-perform, low-cost, non-invasive test method that can be performed in any laboratory, as well as its sequential measurements during the disease course, seem to reflect COVID-19 severity and predict the development of SRF and death. As a result, it could be utilised as a biomarker in risk stratification of the patients in an attempt to promptly identify those who need intensive monitoring, prompt initiation of treatment, and/or inclusion in therapeutic trials.


The objective of this study was to evaluate the efficacy of locking plates versus interlocking intramedullary nails in the treatment of proximal humerus fractures to provide clinical data support and theoretical guidance.P < 0.05 was considered statistically significant.Patients with proximal humerus fracture from the Third hospital of Shijiazhuang city and Third hospital of Hebei medical university and from January 2017 to June 2019 were selected, included and divided into the locking plate group and the interlocking intramedullary nail group according to the intervention received. Information pertaining to the perioperative period  of patients in both groups was collected. VAS pain scores, shoulder activity Constant-Murley scores and postoperative complications were documented. The perioperative data of the two groups were compared, and P > 0.05). However, the average operation time of the locking plate group was shorter than that of the interlocking nail group , and the intraoperative blood loss of the locking plate group (137.4 ± 16.8 ml) was higher than that of the interlocking nail group . There was no significant difference in the VAS score and Constant-Murley score between these two groups at the final follow-up.A total of 64 patients were enrolled, including 36 patients in the locking plate group, with a mean age of 61.3 ± 13.9 years, while the mean age of the interlocking intramedullary nail group was 65.6 ± 11.2 years. There was no statistical difference in gender, affected side, injury mechanism and Neer classification between the two groups (Interlocking intramedullary nails are more minimally invasive than locking plates, but fracture reduction and fixation take longer. There was no significant difference in pain and shoulder function scores between the two internal fixation strategies for the treatment of proximal humerus fracture. Proximal humerus fractures (PHFs) are common fragility fractures in the aging population, occupying about 4–5% of all fractures . The choSurgical strategies for PHFs have gone through a long evolution over the last few decades. The most widely used treatment include open reduction and internal fixation with locking plate osteosynthesis, intramedullary nail fixation, reverse shoulder arthroplasty and shoulder hemiarthroplasty. There is still controversy surrounding the treatment approaches used in displaced PHFs. The locking plate strategy is considered the gold standard treatment for PHFs, but several studies reported an association with several complications . The plaThe aim of this retrospective study was to analyze these two methods, provide clinically referable evidence on the clinical outcomes, and report the complications related to each intervention.We retrospectively analyzed all the patients diagnosed with PHFs between January 2017 and June 2019 in the Third hospital of Hebei medical university and the Third Hospital of Shijiazhuang city. The inclusion criteria were as follows: (1) patients over 18 years of age; (2) two-part, three-part, or four-part of PHFs on Neer classification; (3) fresh fracture; (4) no previous ipsilateral humeral surgery. Meanwhile, the exclusion criteria were as follows: (1) pathologic fractures or open fractures; (2) concomitant neurovascular injury; (3) fractures associated with shoulder dislocation; (4) mental illness. The committee of our institution waived the requirement for written informed consent because this present study was retrospective.The patients were operated under brachial plexus block or general anesthesia. All surgeries were conducted by the same team, which was proficient in both techniques. All patients were lying on a radiolucent operating table in a beach chair position.For the intramedullary nail group, the deltoid-splitting approach was applied. After exposing the deltoid muscle, the anterior and middle deltoid bundles were split bluntly along the direction of the muscle fibers to reach the fracture site. The entry point was revealed after temporary fixation of the fracture fragments with 2.0 mm Kirschner wires, which was 1 cm medial to the greater tuberosity. Then the Kirschner wire was used as a “joystick” to manipulate the humerus head and reduce the displacement. After the tuberosities were reduced, the three- or four-part fracture type would turn into a two-part type. Then the main nail (Targon nail) was inserted, ensuring that the end of the intramedullary nail was 2–3 mm below the cartilage of the humeral head. At last, the proximal and distal screws were locked.For the locking plate group, the classical deltopectoral approach was applied. Both the indirect and direct reductions were performed to reduce the fracture fragments with the assistance of the C-arm. The bone defect of the humeral head was evaluated, and autologous or allogeneic iliac bone grafting was used for patients with poor bone quality and larger defects to increase the stability after plate fixation. At least five locking screws were inserted proximally, with a minimum of 3 distal screws. The nonabsorbable sutures passed through the holes on the plate  and were knotted to repair the rotator cuff and increase its stability.Clinical data and radiographic materials of all the included patients were collected, including gender, age, injury type, comorbidities, operation time, time to surgery, blood loss, and Neer classification . The visShoulders were immobilized for four weeks with an abduction pillow sling. Passive movement of the shoulder began on the second day after surgery. Active movements started 4–6 weeks postoperatively.Clinical follow-up was conducted by two orthopedics attending physicians at 1 and 3 months after surgery. Postoperative plain radiographs were taken at each follow-up. Furthermore, all surgery-related complications were recorded, such as screw breakage, superficial infection, fat liquefaction, varus deformity, delayed union, and acromion impingement.t test were applied to analyze continuous variables. A value of P less than 0.05 was considered statistically significant.All statistical analyses were performed using IBM SPSS Statistics for Windows, version 20.0 . The distributions of all variables were evaluated for normality using the Shapiro–Wilk test. Data that satisfies normality were presented as the mean ± standard deviation. Those data that did not meet normality were presented as medians and quartiles. Chi-squared test were used to analyze the difference in gender distribution, Neer classification of humeral head fractures and injury mechanism between the two groups. The nonparametric test and Student P > 0.05). The average surgery time was shorter in the locking plate group compared to the intramedullary nail group . The blood loss was 137.4 ± 16.8 ml in the locking plate group, which was higher than in the intramedullary nail group . There was no difference in the VAS score (P = 0.202) and Constant-Murley score (P = 0.067) at the final follow-up, as shown in Table In total, 103 proximal humerus fracture patients were searched during this period (January 2017 to June 2019). All the patients were evaluated by two surgeons according to the inclusion and exclusion criteria. After screening, 38 patients were excluded. Sixty-five patients with locking plates and interlocking intramedullary nails were primarily included, 1 of whom was lost to follow-up. The demographic data of these two groups are displayed in Table P = 0.343), as shown in Table The incidence of general complications was 8.33% (3 patients) and 10.71% (3 patients) in the locking plate and intramedullary nail group, respectively  were used in this trial. The entry point of the second-generation nail was more medial to the greater tuberosity Fig. , which iDuring the fixation of PHFs with interlocking intramedullary nails, Kirschner wires are often used to hold the bone fragments in a limited incision for closed reduction –16. HereGardener first proposed medial support to avoid loss of the reduction . BesidesThere are several limitations to our study. Firstly, this is a retrospective, non-randomized study and all the surgeries were performed by the same surgical team. Secondly, the bone mineral density of every patient was not evaluated. However, the mean age of these two groups showed no statistical significance. Thirdly, long-term complications such as humeral head necrosis might have been overlooked since the mean postoperative follow-up was only 9 months .The interlocking intramedullary nail approach is less invasive compared to the use of locking plates but takes longer to achieve fracture reduction and repair. There was no significant difference in pain and shoulder function scores between the two internal fixation approaches for the treatment of proximal humerus fractures. Detailed preoperative evaluation and accurate intraoperative operation, combined with the clinical experience of orthopedic surgeons, can improve the postoperative satisfaction of patients by designing individualized surgical plans and enhancing postoperative functional exercise guidance.


The present work analyzes the influence of modified, epoxidized and maleinized corn oil as a plasticizing and/or compatibilizing agent in the PLA–PHB blend (75% PLA and 25% PHB wt.%). The chemical modification processes of corn oil were successfully carried out and different quantities were used, between 0 and 10% wt.%. The different blends obtained were characterized by thermal, mechanical, morphological, and disintegration tests under composting conditions. It was observed that to achieve the same plasticizing effect, less maleinized corn oil (MCO) is needed than epoxidized corn oil (ECO). Both oils improve the ductile properties of the PLA–PHB blend, such as elongation at break and impact absorb energy, however, the strength properties decrease. The ones that show the highest ductility values are those that contain 10% ECO and 5% MCO, improving the elongation of the break of the PLA–PHB blend by more than 400% and by more than 800% for the sample PLA. Nowadays, polymeric materials have replaced a significant part of the different materials employed in the engineering sector , as well2 emissions which directly increase global warming and destroy ecosystems [These resources, mostly of petrochemical origin, are obtained from non-renewable and limited sources which increase their depletion and the price of energy resources . Additioosystems . Anotherosystems ,12. The osystems . Therefore, one conceivable solution for this massive problem is the recycling and reuse of these materials with the aim of using less virgin material . This isOne of the most widely used biodegradable materials today is polylactic acid (PLA) ,17. PLA Due to the brittleness of PLA, it is often modified with other polymers: thanks to the compatibility of PLA, it can be blended with other polymers to improve its properties. In addition, such a combination can also have other benefits for both polymers, so it is interesting to make such modifications. Some of the petroleum-based materials with which PLA has good miscibility are polyethylene terephthalate (PET) ,24, polyBecause of the aforementioned problems, biopolymers for blending with PLA such as polyhydroxyalkanoates (PHAs) ,34,35, pPlasticizers, low-molecular-weight molecules that generally improve the ductility and processing of polymers, can be used to improve the miscibility between materials. There are two types of plasticizers, depending on their origin, namely petrochemical, such as tar pitch polymerization resins, etc. Some of these are used because they are environmentally friendly and non-toxic plasticizers, such as poly (ethylene glycol) (PEG) ,44,45,46Overall due to PLA’s compatibility, it can be blended with other polymers such as poly-B-hydroxybutyrate (PHB) ,59,60, aThus, the aim of the work was to improve the properties of PLA by blending it with PHB at 75–25%, respectively, to improve the miscibility and reduce the melting temperatures to promote its use in certain industries. For this purpose, different percentages of epoxidized corn oil and maleinized corn oil, 1, 2.5, 5, 7.5, and 10 wt%, were used as plasticizers. The processes of the maleinization and epoxidation of vegetable oils provide greater reactivity to the oil and greater thermal stability with respect to unmodified oils. Therefore, the compatibility of the oils with PLA is improved and the plasticizing effect is increased ,61. Thes−3. The PLA–PHB blend containing 25% PHB was supplied by Biomer  in pellet form with a density of 1.25 g cm−3 with commercial grade P226E. The vegetable oil used to carry out the epoxidation and maleinization process was food-grade corn vegetable oil (CO—corn oil).Poly (lactic acid), PLA commercial grade Biopolymer 2003D, was supplied by Nature Works LLC  in pellet form with a density of 1.24 g cmThe corn oil modification processes were carried out in a three-necked round bottom flask with a capacity of 500 mL in order to incorporate all the necessary elements. One of them was used to introduce the reagents, another one for temperature control and the central one to connect the reflux condenser.The epoxidation process started by adding 182.0 g of corn oil into the flask until 50–55 °C was reached with magnetic stirring. Then, 18.64 mL of acetic acid was added until the temperature was stable at 60 °C, then a mixture of 182.70 mL of hydrogen peroxide (3:1 M ratio (peroxide:oil)) with 1.46 mL of sulfuric acid was added dropwise, and the slow addition of this mixture was performed to avoid an exothermic reaction and with the heating mantle off. Once the addition of this mixture was finished and the reaction was controlled, the working temperature was increased between 80 and 85 °C for 8 h. Samples were collected at each hour of the epoxidation process according to ASTMD1652-97  and ISO c is the exact concentration of the KOH standard solution used (mol-L−1), V is the volume of the KOH standard solution used (mL), and m is the analyzed mass (g). A schematic representation of the maleinization process can be seen in The maleinization ratio used was 2.4:1, following the recommendations of previous works ,66. A toThe samples used in the different experimental techniques and tests were obtained by mixing processes in the laboratory. Before handling the PLA and PHB, both materials were dried at 60 °C for 24 h to eliminate the percentage of moisture indicated by the supplier.First, different mixtures were made with 75% PLA, 25% PHB and different percentages of epoxidized and maleinized corn oil, as shown in To achieve homogeneity in the mixtures, an extrusion process was carried out. The temperature range program used for the different zones of the extruder was the following: 175–180–180–185 °C, from the hopper to the nozzle, respectively, at constant speed of 40 rpm. At the end of the extrusion process, the material was cut until it was reduced to pellet size.Subsequently, the material in the pellets form was injected to obtain standard specimens for subsequent characterization. The chosen temperature program was 175–180–185 °C, from the hopper to the nozzle, respectively. The temperatures used in the manipulation process were those recommended by the material supplier.−1, at room temperature. For the tensile test, the parameters defined in the ISO 527-1:2019 standard [The mechanical characterization was carried out with tensile, flexural, impact, and hardness tests. The tensile and flexural tests were performed on an ELIB 30 universal testing machine . A minimum of five different specimens were tested using a 5 KN load cell. The speed used in the tests was 5 mm minstandard  were folstandard  was usedTo determine the amount of energy absorbed by the material in the case of impact, the test was carried out with a 6 J Charpy pendulum . Five measurements have were taken, with bending type specimens and without notch. The parameters followed in the test are those defined in the ISO 179-1:2010 standard .Finally, the materials surface hardness was measured. Five measurements were taken at different points of the surface of several specimens. A Shore D scale hardness tester, JBA S.A. model 673-D , was used. The parameters followed in the test are those defined in the ISO 868:2003 standard .−1 until the penetrator penetrates 1 mm into the sample. For the HDT test, procedure B of the ISO 75-1:2013 standard [−1 until reaching 0.31 mm of deformation.To evaluate the effects of temperature on the mechanical properties of the materials, a study of softening temperature (VICAT) and heat deflection temperature (HDT) was carried out. Both tests were carried out with a Metrotec model . The parameters for the VICAT test were those of the B50 method, as defined in the ISO 306 standard . The stastandard  was used−1 in a nitrogen atmosphere with a nitrogen flux of 66 mL min−1. With this technique, the glass transition temperature (Tg), cold crystallization peak (Tcc), and the melt peak temperature (Tm) of the PLA blends formulations were identified. The degree of crystallization (X%) was calculated with the formula by Equation (2).−1) [The materials’ miscibility was evaluated through the analysis of their thermal properties, using the differential scanning calorimetry technique (DSC). The thermoanalytical tests were carried out in a Mettler Toledo 882e . The weight range of the samples was 5–10 mg, with an initial heating program from −50 to 180 °C to remove the thermal history, followed by a cooling program from 180 to −50 °C, and finally a second heating program from −50 to 220 °C, at a heating rate of 10 °C min3 J g−1) , and WPL−1, with a constant nitrogen flow of 30 mL min−1.Samples were tested by thermogravimetric analysis. The thermogravimetric analysis (TGA) was carried out in a TGA PT1000 equipment from Linseis Inc. . The analyzed samples, with an average weight between 15 and 20 mg, were subjected to a temperature program from 30 °C to 700 °C at a speed of 10 °C minThe morphology of the blends was analyzed with a ZEISS ULTRA microscope from Oxford Instruments  using a 1.5 KV accelerating voltage. The analyzed samples were the broken impact test specimens, which were sputtered with a thin layer of platinum, using a Leica Microsystems  EM MED0200 high vacuum sputter coater.D) was calculated in percentage with the following equation:im is the initial dry mass of the test material and rm is the dry mass of the residual test material recovered from the sieving.The study of the materials’ disintegration behavior, under composting conditions, was carried out according to the ISO 20200:2015 standard . The tesThe epoxidation of corn oil was performed with a peroxide-to-corn oil molar ratio of 3:1, according to previous experience in the epoxidation process of other vegetable oils . The epoAt the end of the process, at 8 h, an oxirane oxygen index of 5.82 was obtained. Comparing this result with the theoretical rate, obtained from the amount of fatty acids in the corn oil, a conversion of 85.9% was achieved. In addition, the conversion of double bonds represented by the iodine index rapidly decreased during the first 2 h from values close to 140 until the end at 1.5 after 8 h of treatment, which reflects a greater decrease in double bonds than that reflected by the oxygen oxirane. This is due to reactions parallel to the conversion of double bonds into epoxy groups . Analyzi−1 and at the end of the first hour at 180 °C, it is observed that it increases up to 24.4 mg KOH g−1, indicating that the maleinization reaction is occurring. After the second hour, at 200 °C, another large increase is observed, reaching an AV of 87.8 mg KOH g−1, and finally, after the last stage, at 220 °C, the AV reaches 109.2 mg KOH g−1. These results are in total agreement with values obtained by A. Perez-Nakai et al. with an AV of 105 for the maleinized hemp seed and 130 for the maleinized Brazil nut at the end of the epoxidation process [−1 [ process . In addicess [−1 .PLA is a brittle material, and with the intention of improving this characteristic, mixtures were made with PHB. Moreover, different percentages of MCO and ECO were used as plasticizers and compatibilizers. The tensile strength, elongation at break and impact absorbed energy values of the studied materials are represented in Both plasticizers achieved an increase in the ductility of the initial formulation, as can be seen in the values of the elongation at break, toughness modulus, and impact absorbed energy. In the case of the tensile strength, a variation was observed, with the increasing percentage of plasticizer in the formulation, decreasing tensile strength values were obtained. The values of Young’s modulus obtained a variation, although in both cases, with values above the initial formulation. Additionally, both plasticizers managed to reduce the maximum flexural strength of the initial formulation, in such a way that the higher the plasticizer percentage, the lower the flexural strength values. In the case of flexural modulus, both plasticizers increased these values, except for the formulation with 10 wt% of MCO.Regarding the thermo-mechanical properties, as shown in max), which corresponds to the peak of the first derivative curve, and the endset (T90%), which indicates the temperature at which a 90% weight loss occurs. Neat PLA possesses a thermal stability value with a T5% of 311.3 °C, a Tmax of 330.5 °C, and a T90% of 342.6 °C. However, by adding PHB to PLA, the Tmax value increases considerably (by approximately 20 °C), whilst the addition of certain amounts of ECO or MCO to blend (B) formulations causes a slight decrease in the T5%, T90%, and Tmax values. In both modified oils, these values are lower when the quantity is larger. These values are lower for the formulations with MCO. For example, the addition of 10 phr of ECO (B-10ECO) results in a T5% reduction of 15.5 °C, while with 10 phr of MCO (B-10MCO), the reduction is 21.3 °C with respect to the B formulation value (286.1 °C). Regarding the Tmax temperature, it can be observed that both plasticizers lead to a decrease in temperature, obtaining the lowest values at approximately 20 °C and 26 °C lower for B-10ECO and B-10MCO, respectively. A similar tendency was observed by Garcia-Campo et al. [max by 20 °C. For the specific case of maleinized oils, the work of Perez-Nakai et al. [max by 10 °C with respect to the value of neat PLA.The thermal stability of the PLA, PLA–PHB blend, and plasticized formulations with different contents of ECO and MCO was assessed by thermogravimetry analysis (TGA). o et al.  for PLA/i et al.  shows hog) of 61.3 °C, a cold crystallization temperature (Tcc) of 121.9 °C, and a melting temperature (Tm) of 151.2 °C. Both plasticizers—ECO and MCO—decrease the Tg of PLA, which indicates an increase in the mobility of the polymer chains at lower temperatures, evidencing the plasticizing effect of both modified oils [g of up to almost 10 °C for the specific case of B-2.5MCO and in reference to the formulation B. The same plasticizing effect was observed by Dominguez-Candela et al. [Regarding to the DSC results, ied oils . Howevera et al. , who empcc peak is observed at higher temperatures with the incorporation of ECO or MCO. In fact, the Tcc peak temperature increases from 121.9 °C (neat PLA) to 127.1 °C for the B-7.5ECO formulation. This is due to the steric impediment exerted by the ECO on the PLA chains.With respect to crystallinity, it is observed that PLA without plasticizing has a crystallinity of 7.1%, whereas as PHB is added, the PLA is totally amorphous. The PHB molecular chains intercalated between the PLA chains do not allow the PLA chains to be ordered. The incorporation of ECO or MCO shows a slight increase, however, the values are negligible. The TIn this characterization technique, the breaking surface of the specimens was observed, in this case, as those obtained in the impact test. The PLA morphology, as shown in The morphology of the fracture surface of the blends containing MCO can be seen in As was verified by the mechanical properties of the different blends, the saturation of the oil negatively affects the ductile properties of the blends. In the PLA–PHB–ECO system, the sample with the best ductile behavior is the sample with 10 phr of ECO. However, in the PLA–PHB–MCO system, saturation occurs at lower amounts of oil, at approximately 5 phr of MCO, which has a similar morphology to sample B-10ECO. Therefore, to obtain the same plasticizing effect, it is achieved with less amount of MCO than ECO.Finally, to evaluate the disintegration behavior of the developed materials, they were buried in a composting reactor carried out at a laboratory scale. The variation of the mass loss of the different materials under composting conditions can be seen in This work analyzes the usefulness of the use of modified—epoxidized (ECO) and maleinized (MCO)— corn oil as plasticizing and/or compatibilizing agents of the blend 75 wt% PLA–25 wt% PHB. Both chemical modifications of corn oil were carried out at the laboratory level and both processes were carried out correctly according to the results obtained in the analysis of the number of oxirane oxygen and iodine number for the ECO and according to the evolution of the acid number value for the MCO.The incorporation of both modified oils, ECO and MCO, allows to obtain PLA–PHB formulations with better ductile properties, requiring less MCO to achieve the same plasticizing effect as with ECO. The plasticizing effect was observed by differential scanning calorimetry due to the decrease in the glass transition temperature (Tg), decreasing by approximately 2 °C when using ECO and between 4 and 8 °C when using MCO in the PLA–PHB blend. Additionally, the plasticizing effect is observed to a greater extent in the mechanical properties, since the elongation at break and the impact absorbed energy improve considerably when using the oils in the PLA–PHB formulations, increasing the elongation at break by more than 400% when using 10% ECO and 5% MCO. The FESEM analysis reveals a particular morphology of the samples plasticized with oil, presenting spherical cavities dispersed in the matrix and that increase with the increase in oil in the formulations. Finally, the oils delay the disintegration in composting conditions with respect to the PLA–PHB formulation, delaying said degradation to a greater extent than the ECO and it is also affected by the amount of oil used.Therefore, although for this specific study, the MCO shows better plasticization and compatibilization results, two new oils with greater commercial potential were obtained by chemical modification. Compared to other oils obtained from cereals or seeds, CO presents a higher abundance and greater stability against oxidation, which makes it a very interesting raw material from the industrial point of view for applications in both bio-based and synthetic polymers.


Valproic acid is an antiepileptic drug used in different fields of Psychiatry. It is known mostly for its use in managing patients with bipolar affective disorder. In psychiatry of addiction, there is still no approved indications for its usage, but it is widely prescribed in treating alcohol and cocaine abuse, due to the existence of studies in these addictions.This review aims to clarify the relation between valproic acid and dependences, particularly cocaine.Non-systematic literature review using a PubMed search, using the following key words: “valproate”; “cocaine use”.Cocaine dependence can decrease GABA levels in humans. Valproic acid has multiple mechanisms that favour the synthesis of GABA, potentiating its release and postsynaptic GABAergic response. Because of this, valproic acid was found effective in promoting abstinence and in reducing the use of cocaine. There are studies that support the valproic acid’s use in alcohol and cocaine dependences. Valproic acid has been shown to be promising in relapse prevention. It has also showed efficacy in the management of impulsivity and irritability, what makes it useful in managing patients with borderline personality disorder – patients at higher risk for alcohol or substance use disorders.Cocaine addiction involves different phenomena and may respond to distinct pharmacologic approaches. Although some studies need to be confirmed by larger clinical trials, valproic acid seems a promising agent as one of some potential treatments for cocaine dependence. Further studies are required in this field to come to more reliable conclusions.No significant relationships.


To determine the prevalence of mouth breathing children at the santo amaro project/ esef/ upe, and study their main facial and behavior alterations.transversal study.there were 150 children in the sample, with ages ranging from 8 to 10 years. Data was collected by means of a questionnaire and clinical examinations. As for their breathing assessment, two tests were carried out: test 1- breath steam against a mirror; and test 2 - water remains in the mouth with lips closed for 3 minutes.mouth breathing prevalence was of 53.3%. There was no significant difference between gender, age and type of breathing. Facial alterations were: incomplete lip closure , fallen eyes (40.0% X 1.4%), High palate (38.8% X 2.9%), Anterior open bite (60.0% Versus 30.0%), Hypotonic lips (3.8% X 0.0%), Circles under the eyes (97.5% Versus 77.1%).high mouth breathing prevalence without significant statistical difference between genders, age and type of mouth breathing. There was no association between behavior characteristics and type of breathing. There were significant differences between physical traits and breathing pattern. Breathing is one of the vital functions of the human bodyAccording to the literature, it is rare to have exclusive oral breathing; commonly, patients have a mixed respiratory pattern: partially oral and partially nasalFew are the papers related to the prevalence of oral breathing in the literature, and they present percentages that vary from 5%Depending on how long it lasts, oral breathing may cause functional, structural, pathological, postural, occlusal and behavioral alterationsAs physical consequences, the oral breathing child has many physical traits: long face, dropped eyes, dark spots underneath the eyes, open lips, hypotonic and dry lips, narrow nostrils, hypotonic cheek muscles, high palate, narrowing of the upper arch, and occlusal relation tending to Angle's Class IIAs to behavioral alterations, we stress: restless sleep, irritability, difficulty concentration followed by a reduction in school performance and impaired sports skills, amongst othersMiddle and long run alterations, accruing from these alterations, may have harmful consequences for the individual's quality of life due to its personal, physical, psychological and social impactsKnowing the importance of epidemiological research today, working to reduce populational health problems, this paper aims at contributing to the study of oral breathing, through research about its prevalence and main facial and behavioral alterations associated to this respiratory pattern in school children. The participants in this study are enrolled in the Projeto Santo Amaro da Escola Superior de Educação Física (ESEF).This study was carried out at the Escola Superior de Educação Física (ESEF) of the University of Pernambuco (UPE) from June to August, 2005 and is a transversal and observational type of study.Our sample included children regularly enrolled in the Santo Amaro Project. Their ages varied between 8 and 10 years, because dental and facial alterations in the oral breather are already present at this age rangeThe total sample comprised 236 children; throughout a sample calculation, the necessary sample size for this study was 147 children. Thus, the number of subjects per age range was of 50 children, adding up to a total of 150.The sample was picked by randomly selecting the students in the aforementioned age ranges. Sample inclusion criteria were: children between 8 and 10 years of age, from both genders. Sample exclusion criteria were: Children who refused to participate; Children who were not properly authorized by their parents/guardians to participate and they did not sign the Informed Consent form; children with severe respiratory disorders.In order to collect data in order to fulfill the objectives of the present study, we used an identification form for the children, a questionnaire to identify the behavioral alterations of the oral breather, and another form about facial alterations observed at visual inspection, and the results of the tests applied aiming at completing the diagnosis of oral breathing. Clinical exams were carried out by the investigators, using PPE  and the information gathered was recorded in the standardized forms.Test 1:the mirror was placed underneath the child's nostrils and we checked for steam build up in the mirror face (upper or lower) due to breathing. Steam on the upper face indicated nasal breathing and on the lower or lower/upper face indicated oral breathingTest 2:we asked the child to put some water in her/his mouth and kept the lips closed, without swallowing the water, for 3 minutes, and we observed through the lips commisure if there was any effort along the time. The children who were unable to keep their lips closed were considered oral breathersIn order to analyze facial alterations, we checked to see whether or not the children had the following clinical signs: elongated face, dropped eyes, dark circles underneath the eyes, thin upper lip, dry lips, hypotonic lips, everted lower lip, narrow nostrils, high palate, inadequate lip sealing and anterior open bite. In order to assess some of these criteria, we were careful enough as to observe the children in their natural environment, without letting them see that they were being observed. The children who participated in the study underwent the mirror test and mouth moisture test to aid the diagnosis as follows:In order to consider a child as an oral breather, she/he should have at least 3 facial alterations, or steam in the lower mirror face and/or in both mirror faces, or spend less than 3 minutes with water in their mouthsFor statistical analysis purposes, the children were assigned into two groups: nasal breathers and oral breathers, the latter also comprised those children with mixed breathing or exclusive oral breathers.Calibration was carried out in four phases, intra-examiner and inter-examiner, using pictures of the children.In order to carry out data analysis we obtained absolute and percentage distributions (Descriptive Statistics Method), and used the Pearson's Chi-Squared test (or Fisher's Exact test when there was no favorable condition to use the Chi-Squared test) and the equality in two proportions in independent group testing .The significance level used in the statistical test was of 5% (0.05) and the intervals were obtained considering a 95.0% confidence interval. Data were plotted in the Excel spreadsheet and the software used to obtain the statistical calculations was the SAS  version 8.Among types of breathing patterns, it is possible to see that the percentages of facial alterations were correspondently higher among children who were oral breathers when compared to the nasal breathers. It may be established that the percentage differences presented in a descending order were recorded for: inadequate lip sealing (58.8% versus 5.7%), dropped eyes (40.0% x 1.4%), high palate (38.8% x 2.9%), anterior open bite (60.0% versus 30.0%), hypotonic lips (23.8% x 0.0%) and dark circles underneath the eyes (97.5% versus 77.1%).Through the statistical analysis we see the significant difference between the two types of breathing, at the level of 5.0%, for all the items to which we could apply the comparative test (p < 0.05).Assessment of the breathing tests results: Glatzel plate and water in the mouthAs to the test about the time through which the child kept the water in the mouth and the lips sealed, we could see that most of them (86.7%) went up to 3 minutes, and this number was 25.0% higher among the nasal breathers investigated (100.0% versus 75.0%), and such difference reveals a significant relation between the two types of breathing, as far as test 2 is concerned (p < 0.05).In diagnosing a respiratory problem, it is of fundamental importance to obtain information from the parents/guardians during the medical interview. Therefore, questions about the child's sleep patterns, if he/she sleeps with the mouth opened, if there is noisy breathing, if the child lacks concentration at school, if the child feels sleepy during the day, if the pillow is wet in the morning; these questions should all be recorded, because they represent important elements in the diagnosis of oral breathingNotwithstanding, these data alone are not enough for an accurate diagnosis of those mouth breathing individuals, and that is why it is also important to carry out the Glatzel metal plate test and the time through which the child keeps water in her/his mouth with the lips sealed and without swallowing it, since we have seen that the results differ and complete each other.As to the prevalence of oral breathing, despite the few studies that have been carried out with this purpose, we have seen disagreements in the literature. In the present study we noticed that most of the children (53.3%) were considered oral breathers. The highest percentages of this alteration were seen in a study about oral suction habits in a low income population, which was of 77.78%These percentage differences may be justified by the diagnostic criteria and the different methodologies used in the studies. In this investigation, we did not record exclusive oral breathers, gathering both the exclusive oral breathers and the mixed breathing children in the same group, as advocated in the literature. However, some studies did not specify the criteria adopted in details.According to many authorsAs to gender, we noticed that despite a higher percentage seen in males (53.75%) when compared to females (46.25%), this difference was not statistically significant among oral breathers, and such data corroborate other studies in which there was a slight difference in the variable being analyzed8. On the other hand, other investigations reported that there is a slight predominance of this pathology in females when compared to malesAs to facial alterations that affect oral breathers, the highest percentages seen in the present study were: anterior open bite (60%), inadequate lip sealing (58.8%) and high palate (38.8%). These results are in agreement with those from a study in which the main craniofacial alterations seen in oral breathers were: open bite, high palate, malocclusionOther alterations such as dark spots underneath the eyes (97.5%) and dropped eyes (40%) which represented high percentages among the population studied were also mentioned by other authors as being facial alterations commonly found in patients with oral breathing syndromeAmong oral breathers and nasal breathers, respectively, the percentage differences seen in descending order were: inadequate lip sealing (58.8% versus 5.7%), dropped eyes (40.0% x 1.4%), high palate (38.8% x 2.9%), anterior open bite (60.0% versus 30.0%), hypotonic lips (23.8% x 0.0%) and dark spots underneath the eyes (97.5% versus 77.1%).In the long run, individuals who have trouble breathing may develop a number of disorders, such as: craniofacial alterations (long and narrow face), malocclusion, high palate, hypotonic lips and tongue, dry lips, sleepy face, deep dark spots underneath the eyes, greater likelihood of developing dental cavities, speech disorders, postural and gait alterations, all which interfere in school and work performance, and also in social relationshipsAnalyzing the data from the present study, it was also possible to see that of the facial alterations seen, percentages were correspondingly higher in oral breathing children than in nasal breathers, with a significant association, in agreement with the results found by aforementioned authors, despite the fact that these data support the statement that not all individuals with oral breathing patterns present these characteristicsNotwithstanding, today, oral breathing is one of the most concerning problems for public heathConsidering the high prevalence of oral breathing in the population studied, we submit that health policies should be implemented in order to improve the life quality of oral breathing children, and we stress the need for new studies with a larger number of children.1.The prevalence of oral breathing was high, without significant difference between genders.2.There were no relations between breathing pattern and behavioral alterations.3.Physical characteristics related to oral breathing were: elongated face, dropped eyes, dark spots underneath the eyes, narrow nostrils, inadequate lip sealing, dry and hypotonic lips, narrow upper lip (thin), anterior open bite and high palate.